Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study

Background CARTITUDE-1 is a phase 1b-2 study evaluating ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma. Primary efficacy outcomes have previously been reported. Here, we report health-related quality of life (HRQOL) secondary outcomes evaluated using patient-reported outcomes. Methods This single-arm, open-label, phwase 1b-2 study was done at 16 centres in the USA. Patients were aged 18 years or older with diagnosis of multiple myeloma and Eastern Cooperative Oncology Group performance status of 1 or less with three or more previous lines of therapy, or were double refractory to a proteasome inhibitor and immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0 center dot 75 x 106 CAR+ T cells per kg) was administered 5-7 days after lymphodepletion. Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30-item, pre-specified items from the EORTC myeloma module, and EuroQol five-dimensional descriptive system questionnaire. Clinically meaningful changes in patient-reported outcomes were defined by anchor-based minimally important differences. This trial is registered with ClinicalTrials.gov, NCT03548207. This trial is completed but feeding into a long-term follow-up study. Findings Between July 16, 2018, and Oct 7, 2019, 78 patients were enrolled and underwent apheresis in phase 2 of the study. 68 patients were treated (43 [63%] male, 49 [72%] White), and their patient-reported outcomes assessed (median follow-up 16 center dot 9 months, IQR 15 center dot 7-17 center dot 5). After infusion, a transient decline was observed, followed by improvements in global health status (mean change from baseline to day 464 +8 center dot 0 points, SD 20 center dot 9), physical (+4 center dot 6 points, 21 center dot 1), and emotional functional scales (+1 center dot 9 points, 23 center dot 7) over time, and declines for symptom-based scores (-14 center dot 1 pain, SD 31 center dot 5 and -15 center dot 4 fatigue; SD 29 center dot 5), indicating improved patient HRQOL following treatment with cilta-cel. Interpretation These durable HRQOL improvements are consistent with clinical findings, in which a single cilta-cel infusion led to substantial and durable responses in heavily pre-treated patients with relapsed or refractory multiple myeloma. These results support the use of cilta-cel in patients with relapsed or refractory multiple myeloma.